During the Early Iron Age, Cizre was in the kingdom of Kumme, north of Assyria. In classical antiquity, it was located in Corduene (Kardu). In 19th century scholarship, it was often named as the location of Alexander's crossing of the Tigris in 331 BC, further identified with the Roman stronghold of Bethzabde (Syriac: ܒܝܬ ܙܒܕܝ, Bēṯ Zaḇdai), although Stein (1942) is sceptical of this.

Bethzabde was part of the Roman province of Mesopotamia. The chronicler Msiha Zkha speaks of three bishops of Beth Zabdai in the 2nd and 3rd centuries: Merza, Soubha-liso e Sabtha.[3] In 360 Bishop Theodorus was deported by the Persians, along with the general population, and died as a result of the forced march. Another bishop, Maras, was one of the Fathers of the Council of Chalcedon in 451 and in 458 was one of the signatories of the letter of the bishops of Mesopotamia to Emperor Leo I the Thracian after the death of Proterius of Alexandria.[4][5]

In medieval Islamic tradition, Cizre is the location of Thamanin, the town founded by Noah at the foot of Mount Judi where Noah's Ark came to rest, and a "tomb of Noah" as well as a "tomb of Mem and Zin" can be visited in Cizre. Al-Masudi (d. 956) reports that the spot where the ark landed could still be seen in his time. Benjamin of Tudela in the 12th century adds that ʿUmar ibn al-Khaṭṭāb had made the remnants of the ark into a mosque.

In the 19th century, it was the site of a Kurdish rebellion against the Ottoman Empire.[7]

The mayor of Cizre, Aydin Budak, was arrested in December 2009 as part of the KCK investigation.[clarification needed] In October 2011 he was removed from office by the Ministry of the Interior before his trial had concluded. [9]

The current mayor of Cizre is Leyla Imret. As a 27 year-old woman, she is currently the youngest mayor in Turkey. [10]

In October 2014 least 35 people were killed when Riots broke out in the city over Turkey’s response to neighbouring Syria, blocking Kurdish fighters from crossing the border into Syria.[11] It has lost 17 of its citizens who fought with fellow Kurds in Syria during the Siege of Kobanî.[12]